1. Field of the Invention
The present invention relates to high-performance liquid chromatography (“HPLC”) and, more particularly, to devices, systems, and methods for controlling a plurality of pumps that are injecting analyte samples into an HPLC fluid stream by synchronizing their pump cycle and the switch time of injection.
2. Background Art
Scientific laboratories commonly need to separate chemical compounds on such basis as the compound's molecular weight, size, charge or solubility. Separation of the compounds is often a first step in the identification, purification, and quantification of the compounds. Chromatography or, more specifically, high performance liquid chromatography (“HPLC”) has become the analytical tool of choice for applications as varied as biotechnological, biomedical, and biochemical research as well as for the pharmaceutical, cosmetics, energy, food, and environmental industries.
As advances in technology emerge, manufacturers of HPLC instruments are quick to improve the performance of their product lines. In fact, improvements in one technological area or subsystem typically spurn on advancement in interrelated areas or subsystems. For example, U.S. Pat. No. 6,147,595 to Staal, which is incorporated in its entirety herein by reference, discusses several advantages and disadvantages related to evolving approaches based on new technology.
Currently, there are several pump types commonly used as subsystems with HPLC instruments. For example, HPLC instruments may incorporate reciprocating pumps, syringe pumps, and constant pressure pumps, all of which are known to those of ordinary skill in the art.
Most reciprocating pumps include a small, motor-driven plunger that moves rapidly back and forth in a hydraulic chamber to vary the chamber volume. On the backstroke, the plunger creates a negative pressure that pulls in a solvent and on the forward stroke, the plunger of the reciprocating pump pushes the solvent out to a column. In order to achieve steady flow rate to the column, multiple plungers are employed. The multiple plungers may be employed in series or in parallel to achieve the desired delivery flow and pressure.
During compression of the solvent, however, in the pump chamber, energy is absorbed locally that raises the temperature of the solvent. The localized, thermal effect is proportional to the solvent compressibility, its specific heat, the target pressure, e.g., the desired instrument operating pressure, and the rate at which the solvent is compressed. For many leading edge technology HPLC instruments, high pressure and the limited amount of time to compress the solvent create further adverse localized thermal effects in the pump chamber and elsewhere. For example, heat imparted to the solvent produced by compression is usually dissipated to the surroundings, e.g., pump head ambient temperature, at a rate dependent upon the relative mass and thermal conductivity of the compressed solvent and the surroundings.
In most applications and pressures of up to a couple thousand pounds per square inch (“psi”), the thermal effects of compression are negligible. However, at higher pressures, the thermal effects—especially the localized thermal effects—become more appreciable. Moreover, these thermal effects create errors in the pressure of the compressed solvent because the solvent temperature is elevated during compression compared with its delivery during analysis in the instrument. In other words, once the solvent is compressed to a target pressure, the pressure decays as the solvent temperature moves toward equilibrium with the temperature of the instrument. As a result, typically, the compressed solvent settles to a pressure below the target operating pressure and, thereby, creates a deficit in delivered flow.
Prior art pump control systems lack the required ability to react to the localized thermal effects of solvent compression at higher pressures. So despite the advances of the state of the art, HPLC instruments are lacking in stability and performance. As a result, inaccurate results are still common.
Recognizing the shortcomings of the prior art, a high-pressure serial pump was disclosed in U.S. provisional patent application No. 60/587,381 for a “High Pressure Pump Controller” that was filed on Jul. 13, 2004 and is incorporated herein by reference. High-pressure pumps for use in chromatography applications normally use a reciprocating-type design involving two pistons that operate in corresponding chambers. Depending on the fluidic configuration, there are two main design types: parallel or series. In a parallel design, the two pistons alternate in operation whereby one piston delivers flow while the other intakes new solvent from the solvent source and vice versa. In contrast, with a series design, typically one piston, i.e., the primary piston, intakes solvent from the solvent source and delivers the solvent to the other piston. The other piston, i.e., the accumulator piston, performs most of the solvent delivery to the system. In short, the primary piston refills the accumulator piston rapidly at high pressure when, inevitably, the accumulator piston needs to intake new solvent.
Referring to FIG. 1, a series-type reciprocating pump of a type well-known to the art will be described. A primary pumping actuator 12 comprises a primary chamber 12a with a reciprocating primary piston 12b, which terms will be used interchangeable throughout this specification unless otherwise noted. Similarly, the accumulator pumping actuator 14 comprises an accumulator chamber 14a with a reciprocating accumulator piston 14b, which terms, likewise, will be used interchangeable throughout this specification unless otherwise noted.
The primary piston 12b intakes solvent from the solvent source 18, e.g., by creating a negative pressure, and delivers the solvent to both the accumulator chamber 14a of the accumulator pumping actuator 14 and to the system 15. After solvent is delivered from the primary pumping actuator 12 to the accumulator pumping actuator 14, the reciprocating accumulator piston 14b is at or near the end of its backstroke. When the reciprocating accumulator piston 14b begins its forward stroke, the reciprocating accumulator piston 14b introduces the solvent to the system 15. Check valves 11 and 13 allow fluid, i.e., solvent, to pass in one direction only. As a result, solvent in the primary chamber 12a cannot drain back into the solvent source 18 and solvent in the accumulator chamber 14a cannot drain back into the primary chamber 12a. Respective pressure transducers 17 and 19 measure pressure at the outlet of each chamber 12a and 14a, respectively.
Typically, while the accumulator piston 14b delivers flow to the system 15 at high pressure, the primary piston 12b intakes new solvent from the solvent source 18 and waits until it is time to refill the accumulator chamber 14a before starting its forward stroke. Immediately prior to the time when the accumulator chamber 14a requires refilling, the primary piston 12b begins its forward stroke to compress the solvent. Preferably, the primary piston 12b compresses the solvent to the same or substantially the same solvent pressure that is measured by the accumulator transducer 19, i.e., the system pressure, and is set ready for delivering its solvent to the accumulator chamber 14a. Thus, when the accumulator piston 14b approaches the end of its delivering motion (or stroke), the pump controller (not shown) signals the primary piston 12b to deliver solvent and the accumulator chamber 14a to intake solvent. This operation, known as “transfer” is performed rapidly at high pressure and at a high flow rate and continues until the primary piston 12b completely delivers its compressed solvent to the accumulator chamber 14a and to the system 15 while the accumulator piston 14b is re-filled with solvent and ready to resume its normal delivery.
During transfer operation, while the accumulator piston 14b is intaking solvent from the primary pumping actuator 12, the accumulator piston 14b, obviously, cannot also deliver solvent to the system 15. As a result, to avoid interruption in the flow delivered to the system 15, the primary piston 12b becomes responsible for delivering solvent to the system 15, in addition to re-charging the accumulator chamber 14a. To accomplish this task, necessarily, transfer is performed by the primary piston 12b at a higher plunger velocity so that, in addition to completely delivering compressed solvent to the accumulator chamber 14a, a portion of the solvent is delivered to the system 15. To provide the necessary pressure to serve both the accumulator chamber 14a and the system 15, the primary piston 12a plunger velocity must be greater than the accumulator piston's normal delivery velocity. This is referred to as “over-delivery”, which is the difference between the higher plunger velocity and the normal delivery velocity.
Once the transfer operation is finished, the pump controller signals the accumulator piston 14b to resume normal flow delivery and the primary piston 12b to intake new solvent. This cycle, known as the “pump cycle”, is repeated continuously while the accumulator piston 14b is delivering solvent to the system 15. Pump cycle duration depends mainly on the stroke volume of the primary piston 12b and the delivered flow rate.
The role of the check valves 11 and 13 is easy to understand. The primary check valve 11 allows the primary piston 12b to intake solvent at atmospheric pressure from the solvent source 18, and, further, prevents the solvent from flowing back to the solvent source 18 during compression and delivery. Similarly, the accumulator check valve 13 allows the primary piston 12b to deliver solvent to the accumulator chamber 14a, and, further, prevents compressed solvent from flowing back to the primary chamber 12a when the accumulator piston 14b delivers solvent to the system 15 at high pressure and/or when the primary piston 12b intakes new solvent at atmospheric pressure.
The accumulator pressure transducer 19 measures system pressure and provides the pressure input to a pressure control algorithm (not shown). The accumulator pressure transducer 19 also provides the target operating pressure for the primary piston 12b when the primary piston 12b starts the compression, i.e., forward stroke, of new solvent. The primary pressure transducer 17 measures the pressure inside the primary chamber 12a, so that the stroke of the primary piston 12b is stopped when the pressure reaches the target operating pressure.
Generally, with HPLC, bringing an un-pressurized or relatively low-pressurized sample loop on line causes a significant pressure drop to the system 15. The pressure drop is further worsened when the analyte sample is aspirated into the fluid stream of the sample loop with air gaps to mitigate dispersion of the sample.
Indeed, when the solvent inside the primary piston 12b is compressed, its temperature rises. This temperature increase is referred to as “adiabatic heating” and is eventually lost to the solvent surroundings and to the system 15 (when the primary piston 12b starts delivering to the accumulator chamber 14a and/or the system 15), at a rate dependent on the relative mass and thermal conductivity of the compressed solvent and its surroundings. However, this temperature loss creates an error in the pressure of the compressed solvent, because the solvent temperature and pressure at the time of compression are higher than the temperature and pressure that the solvent will eventually have, i.e., the operating temperature and operating pressure of the system 15.
Therefore, once the solvent is compressed to the target pressure, i.e., system operating pressure, its pressure starts to decay as its increased temperature starts to equilibrate back down to system operating temperature. The compressed solvent pressure eventually settles at a value below the intended system operating pressure, which creates a deficit in delivered flow when the primary piston 12b starts delivering, i.e., “over-delivering” to the system 15. The thermal effect is proportional to the solvent compressibility, to the specific heat of the solvent, to the compression pressure, and to the rate at which the solvent is compressed.
As stated previously, for pressures up to a few thousand psi, this thermal effect can normally be ignored. However, at higher pressures, the thermal effect can be more significant. Furthermore, due to the precision timing involved and required in the reciprocating pumps' action, there is normally a limited amount of time to compress the solvent from atmospheric pressure to system operating pressure. Therefore, this thermal effect creates significant flow delivering errors, which represent solvent composition errors when the solvents of two or more pumps are combined together at high pressure to for in a solvent gradient.
Furthermore, when the outlets of two or more parallel pumps delivering dissimilar solvents are connected together to a common fluid node, it becomes necessary to prevent the control loops from interacting or oscillating when the control periods, which is to say the transfer operation periods, of the pumps overlap, or “collide”.
Isolation restrictors have been proposed to isolate the control loops from external fluid conditions. However, this isolation is not enough for high-precision solvent gradients, where the small remaining interaction between both pump's control loops creates solvent composition errors, i.e., “collisions”.
To eliminate these errors and avoid collisions, it would be desirable to provide devices, systems, and methods that enable the two pumps to interchange information about their respective position within the pump cycle to avoid their control periods overlapping. Thus, when a control period “collision” is foreseen, the pump with a longer pump cycle advances its control period just enough to avoid the overlap with the other pump control period. This technique effectively removes any remaining composition errors in solvent gradients and avoids “collisions”.
Also, it would be desirable to provide control devices, control systems, and control methods to mitigate pressure disturbance that is associated with injection of lower pressure analyte samples into a higher pressure HPLC fluid stream. It would also be desirable to provide control devices, control systems, and control methods to enhance chromatographic performance related to retention time and area reproducibility. It would further be desirable to provide control devices, control systems, and methods to enhance reproducibility of results by forcing a consistent timing relationship between the injection run of the analyte sample, the mechanical position of the pumps' plungers, and the start and subsequent solvent gradient of the analyte sample delivery.